The research outlined in this proposal deals with chemistry and biochemistry involved in the synthesis of toxic metal-alkyls. Recently our group has formulated general mechanisms for the biosynthesis of metal-alkyls which shows a correlation between oxidation/reduction couples and methylation. These metal-alkyls are poisonous to central nervous systems of higher organisms including man. Last year we elucidated mechanisms for methyl-transfer to lead, tin and sulfur. Using fluorescence quenching methods and 270 MHz NMR, we have measured cellular diffusion rates for the neurotoxin methylmercury chloride, and we hope to apply these methods to study transport of other metal-alkyls. We have made substantial progress in understanding the mechanism of action of the B12-enzyme diol dehydrase and ribonucleotide reductase. In vivo studies on ribonucleotide reductase are possible when cells are pre-treated with ether.